Glomerular filtration response to acute loading with protein from different sources in healthy volunteers and diabetic patients


Nakamura, H.; Yamazaki, M.; Chiba, Y.; Tamura, N.; Momotsu, T.; Ito, S.; Shibata, A.; Kamoi, K.; Yamaji, T.

Tohoku Journal of Experimental Medicine 162(3): 269-278

1990


To evaluate the effects of acute protein loading on the glomerular filtration rate, albumin excretion rate and concentration of plasma amino acids, ten healthy volunteers and six type 2 diabetic patients with normoalbuminuria were studied before and after eating 0.7 g/kg body weight of tuna fish, boiled egg white, cheese or tofu (bean curd) on separate days. Furthermore, to study the possible role of glucagon, growth hormone, atrial natriuretic peptide and kallikrein in the responses of glomerular filtration rate to protein, these substances were measured before and after ingestion of tuna fish or egg white in six healthy volunteers. In healthy subjects, glomerular filtration rate increased significantly (p less than 0.01) from 98.1 +/- 4.2 ml/min during the baseline period to 129.9 +/- 6.6 ml/min after ingestion of tuna fish. No significant differences were seen between glomerular filtration rate before and after ingestion of egg white, cheese or bean curd. No significant differences were observed between the baseline albumin excretion rate and that after loading with any of the four kinds of protein. Plasma concentrations of alanine, glycine and arginine (amino acids known to induce glomerular hyperfiltration) increased to a greater degree after ingestion of tuna fish than after administration of the other meals. Diabetic subjects and healthy volunteers had similar responses. Plasma glucagon and growth hormone concentrations increased after ingestion of the tuna fish meal or egg white. Plasma atrial natriuretic peptide concentration and urinary kallikrein excretion were unaffected by ingestion of these two kinds of protein. These findings suggest that responses of glomerular filtration rate to acute protein loading may differ depending on the protein ingested, and that these responses may not be directly induced by glucagon, growth hormone, atrial natriuretic peptide or kallikrein.

Tohoku
J.
Exp.
Med.,
1990,
162,
269-278
Glomerular
Filtration
Response
to
Acute
Loading
with
Protein
from
Different
Sources
in
Healthy
Volunteers
and
Diabetic
Patients
HIROSHI
NAKAMURA,
MASATOSHI
YAMAZAKI,
YASUKO
CHIBA,
NORIKO
TAMURA,
TAKESHI
MOMOTSU,
SEIKI
ITO,
AKIRA
SHIBATA,
KYUZI
KAMOI.
and
TOHRU
YAMAJIt
The
First
Department
of
Internal
Medicine,
Niigata
University
School
of
Medicine,
Niigata,
951,
*
Nagaoka
Red
Cross
Hospital,
Niigata,
940
and
'the
Third
Department
of
Internal
Medicine,
Faculty
of
Medicine,
University
of
Tokyo,
Tokyo,
113
NAKAMURA,
H.,
YAMAZAKI,
M.,
CHIBA,
Y.,
TAMURA,
N.,
MOMOTSU,
T.,
ITO,
S.,
SHIBATA,
A.,
KAMOI,
K.
and
YAMAJI,
T.
Glomerular
Filtration
Response
to
Acute
Loading
with
Protein
from
Afferent
Sources
in
Healthy
Volunteers
and
Diabetic
Patients.
Tohoku
J.
Exp.
Med.,
1990,
162
(3),
269-278
To
evaluate
the
effects
of
acute
protein
loading
on
the
glomerular
filtration
rate,
albumin
excretion
rate
and
concentration
of
plasma
amino
acids,
ten
healthy
volunteers
and
six
type
2
diabetic
patients
with
normoalbuminuria
were
studied
before
and
after
eating
0.7
g/kg
body
weight
of
tuna
fish,
boiled
egg
white,
cheese
or
tofu
(bean
curd)
on
separate
days.
Furthermore,
to
study
the
possible
role
of
glucagon,
growth
hormone,
atrial
natriuretic
peptide
and
kallikrein
in
the
responses
of
glomerular
filtration
rate
to
protein,
these
substances
were
measured
before
and
after
ingestion
of
tuna
fish
or
egg
white
in
six
healthy
volunteers.
In
healthy
subjects,
glomerular
filtration
rate
increased
significantly
(p
<
0.01)
from
98.1
+4.2
ml/min
during
the
baseline
period
to
129.9+
6.6
ml/min
after
ingestion
of
tuna
fish.
No
significant
differences
were
seen
between
glomerular
filtration
rate
before
and
after
ingestion
of
egg
white,
cheese
or
bean
curd.
No
significant
differences
were
observed
between
the
baseline
albumin
excretion
rate
and
that
after
loading
with
any
of
the
four
kinds
of
protein.
Plasma
concentrations
of
alanine,
glycine
and
arginine
(amino
acids
known
to
induce
glomerular
hyperfiltration)
increased
to
a
greater
degree
after
ingestion
of
tuna
fish
than
after
administration
of
the
other
meals.
Diabetic
subjects
and
healthy
volunteers
had
similar
responses.
Plasma
glucagon
and
growth
hormone
concentrations
increased
after
ingestion
of
the
tuna
fish
meal
or
egg
white.
Plasma
atrial
natriuretic
peptide
concentration
and
urinary
kalli-
krein
excretion
were
unaffected
by
ingestion
of
these
two
kinds
of
protein.
These
findings
suggest
that
responses
of
glomerular
filtration
rate
to
acute
protein
loading
may
differ
depending
on
the
protein
ingested,
and
that
these
reponses
may
not
be
directly
induced
by
glucagon,
growth
hormone,
atrial
natriuretic
peptide
or
kallikrein.
diabetic
nephropathy
acute
protein
loading
;
hyperfiltration
;
composition
of
amino
acids
Received
October
9,
1990
;
revision
accepted
for
publication
October
27,
1990
269
270
H.
Nakamura
et
al.
The
presence
of
an
elevated
glomerular
filtration
rate
(GFR)
in
uncomplicat-
ed
type
1
(insulin-dependent)
diabetic
patients
has
been
known
for
many
years
(Mogensen
1971,
1976).
It
was
reported
that
glomerular
hyperfiltration
in
type
1
diabetes
with
early
stage
diabetic
nephropathy
might
be
important
in
the
subse-
quent
development
of
late
diabetic
nephropathy
(Mogensen
1971,
1976).
Although
the
exact
mechanism
inducing
glomerular
hyperfiltration
remains
to
be
elucidated,
many
factors,
such
as
glucose
(Greene
et
al.
1987),
ketone
bodies
(Trevisan
et
al.
1987),
dietary
protein
(Bosch
et
al.
1983,
1984,
1986
;
Jones
et
al.
1985
;
Hostetter
1986
;
Dhaene
et
al.
1987)
and
prostaglandins
(Krishna
et
al.
1988),
have
been
implicated.
It
was
recently
reported
that
a
high-protein
diet
produces
a
significant
increase
in
GFR
(Bosch
et
al.
1983, 1984,
1986
;
Jones
et
al.
1985
;
Hostetter
1986
;
Dhaene
et
al.
1987)
and
that
low-protein
alimentation
might
prevent
the
progres-
sion
of
renal
failure
in
patients
with
diabetic
nephropathy
(Gingliano
et
al.
1986
;
Evanoff
et
al.
1987
;
Wiseman
et
al.
1987).
However,
low-protein
alimentation
should
be
approached
with
caution,
because
hypoproteinemia
was
often
observed
in
protein-restricted
rats
with
renal
failure
(Motomura
et
al.
1988).
To
date,
mainly
animal
proteins
have
been
used
to
study
the
effects
of
acute
protein
loading
on
renal
function.
It
was
reported
that
GFR
increased
after
ingestion
of
animal
proteins
(Bosch
et
al.
1983,
1984,
1986
;
Hostetter
1986).
These
findings,
together
with
the
finding
that
low-protein
alimentation
may
have
the
above-
mentioned
harmful
side
effects,
led
us
to
investigate
whether
diabetic
nephropath-
y
is
influenced
by
the
quality
as
well
as
the
quantity
of
dietary
protein.
In
a
previous
report,
we
examined
the
influence
of
proteins
from
two
different
sources
on
renal
function
in
healthy
volunteers
and
diabetic
subjects
(Nakamura
et
al.
1989).
Our
study
showed
that
ingestion
of
cooked
soybean
protein
does
not
increase
GFR.
This
result
raised
the
possibility
that
not
all
animal
proteins
might
affect
the
GFR.
Therefore,
we
studied
the
effects
of
acute
protein
loading
of
four
different
protein
sources
on
renal
function
in
healthy
volunteers
and
diabetic
patients.
The
exact
mechanism
of
protein-induced
glomerular
hyperfiltration
remains
to
be
elucidated.
It
has,
however,
been
reported
that
glucagon
(Parving
et
al.
1977),
growth
hormone
(Corvilain
and
Abramow
1962),
atrial
natriuretic
peptide
(ANP)
(Fried
and
McCoy
1986)
and
kallikrein-kinin
system
(Levy
et
al.
1977)
induced
glomerular
hyperfiltration.
Another
aim
of
this
study,
therefore,
was
to
examine
the
role
of
these
substances
in
mediating
glomerular
hyperfiltration.
SUBJECTS
AND
METHODS
The
subjects
comprised
ten
healthy
volunteers
(6
men
and
4
women,
aged
49.1+8.9
years,
BMI
22.0+1.9
kg/m
2
)
and
six
type
2
diabetic
patients
(4
men
and
2
women,
aged
48.7+
10.0
years,
BMI
21.9+1.8
kg/m
2
).
All
were
normotensive
and
had
normal
renal
function
as
evidenced
by
normal
serum
creatinine
concentration
and
urinalysis.
Three
Acute
Loading
with
Protein
from
Different
Sources
271
diabetic
patients
were
given
oral
hypoglycemic
agent,
and
the
others
were
treated
with
diet
therapy.
All
diabetes
were
in
resonable
metabolic
control
(fasting
blood
glucose
112.0
+
5.8
mg/100
ml,
HbA
lc
5.9+
0.2%,
normal
range
4.6-5.7%).
Duration
of
diabetes
was
4.4
+
1.0
years.
Protein
loading
tests
were
performed
in
the
fasting
state.
Subjects
began
the
test
by
receiving
oral
hydration
with
400
ml
of
water.
Baseline
and
test
GFRs
were
calculated
from
endogenous
creatinine
clearance.
After
the
baseline
creatinine
clearances
were
measured,
the
subjects
ingested
on
separate
days
0.7
g/kg
body
weight
of
protein
in
the
form
of
cooked
tuna
fish,
boiled,
salted
egg
white,
cheese
or
tofu
(bean
curd)
with
soy
sauce.
The
composition
of
each
test
meal
is
shown
in
Table
1.
After
protein
loading,
the
subjects
ingested
100
ml
of
water
each
hour.
Urine
volume
was
recorded,
and
creatinine
and
albumin
concentrations
in
both
urine
and
plasma
were
measured
hourly
and
the
albumin
excretion
rates
(AER)
were
calculated.
Plasma
amino
acid
concentrations
were
also
measured
before
and
after
protein
loading.
To
study
the
effect
of
protein
loading
on
the
plasma
concentrations
of
glucagon,
growth
hormone
and
ANP
and
on
urinary
kallikrein
excretion,
six
additional
healthy
male
subjects
aged
23
to
28
years
received
acute
loading
tests
of
two
kinds
of
protein
(tuna
fish
and
egg
white).
Plasma
concentrations
of
glucagon,
growth
hormone
and
ANP
were
measured
hourly.
Urinary
concentrations
of
kallikrein
were
also
measured
hourly,
and
kallikrein
excretion
rates
were
calculated.
Measurements
of
albumin
in
urine
were
carried
out
by
double-antibody
radioimmunoas-
TABLE
1.
Composition
of
the
four
test
meals
Tuna
Egg
Cheese
Tofu
Carbohydrates
(g/g
protein)
0.14
0.09
0.09
0.12
Salt
(g/g
protein)
0.11
0.10
0.06
0.10
Water
(g/g
protein)
2.96
8.43
2.76
3.47
Phosphate
(mg/g
protein)
15.4
1.10
31.7
12.5
Amino
acid
(mg/g
protein)
Aspartic
acid
92
110
76
120
Threonine
43
45
35
41
Serine
44
64
50
51
Glutamic
acid
140
140
210
190
Proline
32
36
110
59
Glycine
54
37
18
46
Alanine
66
62
29
47
Valine
48
73
68
56
Cystine
10
31
8
18
Methionine
29
39
27
15
Isoleucine
48
56
53
54
Leucine
80
89
98
89
Tyrosine
37
40
55
43
Phenylalanine
40
60
53
33
Histidine
93
25
31
29
Tryptophan
13
16
13
15
Lysine
87
69
82
68
Arginine
66
59
34
81
272
H.
Nakamura
et
al.
say
according
to
a
method
previously
reported
(Ito
et
al.
1989).
Serum
albumin
levels
were
measured
by
laser
nephelometry.
Creatinine
concentrations
in
urine
and
serum
were
measured
by
Folin's
method.
Plasma
amino
acid
concentrations
were
measured
by
an
auto-analyzer
(System
6300:
Beckman,
Tokyo).
Plasma
glucagon
levels
were
measured
by
double-antibody
radioimmunoassay
using
specific
antisera
against
pancreatic
glucagon
(Sugimoto
1981).
Plasma
growth
hormone
and
ANP
(Yamaji
et
al.
1985)
were
measured
by
radioimmunoassay,as
was
urinary
kallikrein
(PEG
method)
(Kato
et
al.
1980).
The
GFR
was
always
corrected
for
body
surface
area
and
was
expressed
per
1.73
m
2
.
Body
surface
area
was
calculated
from
height
and
weight.
All
data
are
expressed
as
mean
values
+
S.D..
The
significance
between
the
means
was
calculated
using
Student's
t-test
or
Welch's
test.
RESULTS
Renal
response
to
protein
loading
The
results
of
the
protein
loading
tests
are
shown
in
Tables
2
and
3.
In
healthy
volunteers,
GFR
increased
significantly
(p
<0.01)
after
ingestion
of
tuna
fish
:
from
98.1+4.2
ml/min/1.73
m
2
during
the
baseline
period
to
129.9+6.6
ml/
min/1.73
m
2
.
In
diabetic
patients,
GFR
also
increased
significantly
after
tuna
fish
ingestion
(96.7+
6.2
to
130.8+
7.5
ml/min/1.73
m
2
).
No
significant
differences
were
found
between
GFR
before
and
after
ingestion
of
egg
white,
cheese,
or
bean
curd
(Fig.
1).
In
all
subjects,
plasma
concentration
of
serum
creatinine
increased
significantly
after
ingestion
of
tuna
fish
:
from
0.88+0.09
mg/
100
ml
to
1.42+0.10
mg/100
ml.
No
significant
differences
in
plasma
creatinine
concentrations
were
shown
before
and
after
ingestion
of
the
other
three
meals.
No
significant
differences
in
AER
were
observed
before
and
after
loading
with
any
of
the
four
kinds
of
protein.
In
all
subjects,
mean
atrial
blood
pressure
and
blood
glucose
levels
did
not
change
during
study.
TABLE
2.
Changes
in
GFR
(ml
/
min
/
1.73
m
2
)
following
protein
loading
Healthy
subjects
Diabetic
subjects
Meal
Post-meal
Post-meal
Pre-meal
Pre-meal
1
hr
2hr
3hr
1
hr
2hr
3hr
Tuna
98.1
110.6
120.7*
129.9*
96.7
109.1
121.8*
130.8*
+4.2
+5.9
+7.7
+6.6
+6.2
+
7.3
+8.1
+
7.5
Egg
99.0
97.6
100.0
99.5
97.1
98.7
97.2
101.0
+4.6
+3.8
+5.7
+4.7
+5.2
+4.6
+3.6
+4.2
Cheese
98.9
97.9
98.2
98.7
+5.4
+2.9
+3.3
+2.8
Tofu
98.9
94.7 99.7
97.3
+4.5
+5.6
+4.0
+4.0
99.9
97.9
98.1
92.1
+6.1
+7.6
+5.1
+4.8
97.5
97.5
98.4
96.2
+4.2
+5.7
+3.9
+4.6
Values
are
means
+
S.D..
*p
<0.01
vs.
baseline
values.
Acute
Loading
with
Protein
from
Different
Sources
273
TABLE
3.
Changes
in
AER
(pg
/
min)
following
protein
loading
Healthy
subjects
Diabetic
subjects
Meal
Post-meal
Post-meal
Pre-meal
Pre-meal
1
hr
2hr
3hr
1
hr
2hr
3hr
Tuna
7.9
9.9
6.4
6.2
7.9
8.9
7.4
6.5
+5.7
+7.7
+5.0
+4.5
+4.5
+4.1
+3.9
+3.7
Egg
7.1
4.9
5.3
6.6
6.9
5.0
7.3
6.6
+5.9
+3.8
+4.0
+4.2
+4.1
+3.4
+4.8
+4.7
Cheese
6.2
7.2
5.9
7.4
7.2
6.9
5.2
6.4
+3.4
+5.1
+4.6
+5.7
+3.8
+3.9
+2.9
+5.0
Tofu
6.7
8.4
7.4
8.6
6.8
7.1
8.1
8.6
+4.6
+6.3
+6.2
+6.4
+5.3
+4.6
+5.9
+5.7
Values
are
means+S.D..
Healthy
volunteers
Diabetic
subjects
4,
*
*
150
-
100
-
,
A
50
Tuna
Egg
Cheese
Tofu
Tuna
Egg
Cheese
Tofu
Fig.
1.
Chages
in
GFR
following
protein
loads.
GFR
increased
significantly
after
ingestion
of
tuna
fish
meal
(*
*p
<0.01
vs.
baseline
values).
Changes
in
plasma
amino
acids
following
protein
loading
The
results
of
the
plasma
amino
acid
analysis
are
shown
in
Table
4.
Almost
all
amino
acids
increased
in
plasma
after
ingestion
of
each
of
the
four
kinds
of
protein.
Ingestion
of
tuna
fish
caused
significantly
greater
increases
in
plasma
concentration
of
total
amino
acids
than
the
other
meals.
Plasma
concentrations
of
alanine,
glycine
and
arginine,
amino
acids
known
to
induce
glomerular
hyperfiltration,
increased
more
after
the
ingestion
of
tuna
fish
than
after
the
other
meals.
274
H.
Nakamura
et
al.
TABLE
4.
Increases
in
plasma
amino
acid
concentrations
following
protein
loads
Healthy
subjects
Diabetic
subjects
Tuna
Egg
Cheese
Tofu
Tuna
Egg
Cheese
Tofu
1191**
1182**
1079**
±168
±119
±153
0.0**
1.8**
2.2*
+0.5
±0.3
+1.4
18.4**
20.9**
38.5**
+8.8
+7.1
+9.7
69.1
56.2
52.7
+11.7
+13.6
+14.2
15.3**
13.2**
13.9
+7.3
+8.1
+6.5
121.7
102.4
81.8
+32.6
+21.8
+21.2
1998
+189
2.5
+0.4
46.5
+9.0
32.8
+12.8
28.1
+7.9
63.1
+20.8
68.0
+9.4
187.6
+21.0
289.9
+49.2
7.4
+1.5
78.1
+6.4
109.7
+17.4
246.7
+26.4
62.4
+12.4
35.4
+7.1
97.2
+10.6
33.4
+6.8
254.3
+28.4
108.5
+19.6
1062**
1059**
1176**
±167
±148
±196
0.0**
0.4**
1.3**
+0.3
+0.5
+0.3
0.0**
12.9**
28.5**
+2.7
+5.1
+7.2
35.4
27.1
27.5
+14.6
+15.1
+12.0
10.7**
+9.8
39.4**
±
15.5
111.7**
+46.1
1.2**
+1.0
20.6**
+5.1
58.3**
±
11.2
91.3**
+19.0
36.4**
+8.5
0.0**
+3.4
0.0**
+5.8
0.2**
+3.1
51.3**
±
19.9
68.6**
+16.4
25.5**
+8.0
42.5**
+14.9
120.2**
+49.0
2.1**
±1.2
18.8**
±5.6
44.6**
+12.8
105.0**
+18.5
35.4**
±7.2
12.6**
+3.5
0.8**
+6.7
9.9**
+4.8
68.4**
+17.9
57.9**
+15.4
11.3**
+10.8
15.1**
+12.3
136.5*
*
+38.9
0.0**
+0.9
2.9**
+2.4
64.2**
+10.3
102.5**
+13.1
38.3**
+9.1
34.2
+4.9
11.6**
+9.7
12.1**
+5.5
81.9**
+20.6
65.0**
+16.8
9.1**
+5.2
87.2
+29.9
5.2**
+3.6
41.8**
+16.7
142.0**
+40.0
1.0**
+1.3
10.7**
3.5
49.2**
+12.3
100.9**
+21.0
32.5**
±8.7
0.0**
+3.0
0.0**
+6.4
0.0**
±2.1
46.9**
+16.3
49.3**
+15.2
8.8**
+3.4
69.0
+21.5
7.9**
+3.4
35.4**
±13.8
133.9*
*
+40.6
1.6**
+1.0
13.4**
+2.7
48.9**
±16.9
99.9**
+17.8
41.6**
+6.9
11.5**
+6.4
8.7**
+9.8
5.6**
+3.4
79.2**
+19.0
50.8**
+16.8
17.3*
+6.0
56.9
+19.8
0.0**
+0.4
10.3**
+10.6
161.2**
+38.4
0.0**
+0.8
2.2**
+1.9
87.0*
+12.2
114.2**
+12.5
30.4**
±8.8
21.6**
+5.8
5.4**
+4.9
7.3**
+4.7
81.6**
+16.8
50.4**
+16.3
Total
2065
+224
Aspartic
acid
4.5
+1.8
Threonine
127.6
+49.8
Serine
61.8
+12.4
Glutamic
acid
30.6
+9.3
Proline
99.9
+33.1
Glycine
75.0
+17.8
Alanine
167.3
+35.2
Valine
305.3
+51.2
Cystine
6.1
+1.5
Methionine
64.8
+8.0
Isoleucine
149.7
+12.6
Leucine
235.1
+23.3
Tyrosine
61.2
+10.6
Phenylalanine
33.9
+6.2
Histidine
101.0
+13.5
Tryptophan
35.0
+6.2
Lysine
287.0
+25.3
Arginine
121.7
+17.6
Values
are
expressed
as
mean
increases+
S.D.
in
amino
acid
concentration
(nmol/
ml)
above
baseline
values
after
protein
intake.
Different
from
the
respective
tuna
fish
meal
intake
*p
<0.05,
**p
<
0.01.
Acute
Loading
with
Protein
from
Different
Sources
275
TABLE
5.
Changes
in
glucagon,
growth
hormone,
ANP,
and
kallikrein
following
protein
loads
in
normal
volunteers
Tuna
fish
Egg
white
Post-meal
Post-meal
Pre-meal
Pre
meal
1
hr
2hr
3hr
1
hr
2hr
3hr
Glucagon
81.3
125.0*
126.7*
140.7**f
81.0
108.3*
103.2*
102.8*
(ng/ml)
+16.8
+21.4
+20.5
+30.6
+18.7
+25.4
+31.0
+25.4
Growth
0.13
0.18
1.52*f
4.08*
0.45
0.33
0.28
3.27*
hormone
+0.11
+0.15
+1.17
+3.71
+0.71
+0.24
+0.30
+2.83
(ng/ml)
ANP
25.9
24.3
25.4
23.5
31.4
32.4
35.5
36.9
(pg/ml)
+9.8
+7.9
+7.4
+7.2
+5.6
+3.5
+8.1
+7.8
Kallikrein
165.5
171.7
126.7
145.0
149.5
124.8
86.2
118.3
(ng/ml)
+67.7
+99.9
+76.3
+91.9
+42.1
+23.8
+42.2
+99.1
Values
are
means+
S.D..
*
p
<0.05
vs.
baseline
values
**p
<0.01
vs.
baseline
values
fp
<0.05
vs.
values
after
ingestion
of
egg
white.
Hormonal
response
to
protein
loading
Plasma
glucagon
and
growth
hormone
concentrations
increased
after
inges-
tion
of
tuna
fish
or
egg
white
(Table
5).
Plasma
concentrations
of
these
two
hormones
increased
significantly
after
ingestion
of
tuna
fish.
Plasma
ANP
was
unchanged
in
response
to
both
protein
loadings.
Urinary
kallikrein
excretion
was
also
unchanged
following
both
protein
loads
(Table
5).
DISCUSSION
In
the
present
study,
GFR
was
evaluated
on
the
basis
of
creatinine
clearance,
because
evaluation
of
GFR
by
the
radioisotope
method
is
not
legally
recognized
in
Japan.
Some
investigators
have
already
reported
simultaneous
inulin
and
creatinine
clearance
studies
during
a
protein
loading
test
and
results
obtained
by
both
methods
were
comparable
in
patients
without
renal
dysfuction
(Bosch
et
al.
1983,
1984
Dhaene
et
al.
1987).
Based
on
their
findings,
it
seems
likely
that
the
results
of
GFR
found
in
our
study
may
be
reliable.
The
present
study
shows
that
ingestion
of
tuna
fish
caused
a
significant
increase
in
GFR,
whereas
ingestion
of
the
other
three
meals
did
not
affect
the
GFR
in
healthy
volunteers
or
diabetic
patients.
Therefore,
the
effects
of
protein
administration
on
GFR
may
differ
from
one
protein
to
another.
Intravenous
administration
of
alanine,
glycine
and
arginine
increases
GFR.
In
our
study,
plasma
levels
of
these
amino
acids
increased
significantly
only
after
ingestion
of
tuna
fish,
which
caused
an
increase
in
the
GFR.
This
result
suggests
that
increase
of
GFR
after
ingestion
of
tuna
fish
may
be
due
to
increase
of
these
276
H.
Nakamura
et
al.
amino
acids
in
plasma.
However,
ingestion
of
the
other
meals
did
not
induce
increased
plasma
levels
of
these
amino
acids
and
glomerular
hyperfiltration,
despite
the
fact
that
these
amino
acids
are
as
abundant
in
the
other
protein
sources
examined
as
in
tuna
fish.
Furthermore,
these
amino
acids
were
less
contained
in
meat
than
tuna
fish,
though
ingestion
of
meat
induced
hyperfiltration
(Bosch
et
al.
1984
;
Hostetter
et
al.
1986).
The
mechanism
behind
these
phenomenon
remains
to
be
elucidated.
We
cannot
deny
that
these
facts
may
due
to
differences
in
the
intestinal
absorption
of
meals.
Several
mediators
of
the
glomerular
hyperfiltration
observed
after
a
protein
meal
have
been
reported.
Glucagon,
growth
hormone,
ANP
and
kallikrein
induce
glomerular
hyperfiltration.
In
the
present
study,
plasma
glucagon
and
growth
hormone
concentrations
increased
significantly
with
increased
GFR.
However,
plasma
concentrations
of
these
two
hormones
increased
without
glomerular
hyperfitration,
after
administration
of
some
protein.
Furthermore,
despite
glomerular
hyperfiltration,
the
plasma
ANP
concentration
and
urinary
kallikrein
excretion
were
unaffected
by
ingestion
of
two
kinds
of
protein.
These
findings
suggest
that
responses
of
GFR
to
acute
protein
loading
may
not
be
directly
induced
by
these
substances.
Recently,
it
was
reported
that
dietary
protein
restriction
prevented
the
progression
of
diabetic
nephropathy.
However,
a
low-protein
diet
may
cause
hypoproteinemia,
muscle
wasting,
or
malnutrition
(Kleinknecht
et
al.
1979
;
Motomura
et
al.
1988).
Moreover,
it
has
been
reported
that
not
all
proteins
equally
induce
glomerular
hyperfiltration
(Dhaene
et
al.
1987).
These
facts
led
us
to
investigate
whether
diabetic
nephropathy
was
influenced
by
the
quality
as
well
as
the
quantity
of
dietary
protein.
Our
previous
study
showed
that
acute
administration
of
vegetable
proteins
(at
least
of
cooked
soybean
protein)
did
not
increase
GFR
(Nakamura
et
al.
1989).
In
addition,
the
present
study
demon-
strates
that
ingestion
of
cheese
or
egg
white
does
not
induce
hyperfiltration.
It
seems
probable,
therefore,
that
these
proteins
can
be
exempted
from
dietary
protein
restriction.
However,
as
our
study
involved
only
acute
loading,
pro-
longed
clinical
investigation
is
necessary
to
evaluate
the
possibility
mentioned
above.
In
prolonged
diet
therapy,
the
phosphorus
content
of
cheese
or
bean
curd
should
be
taken
into
consideration,
because
phosphorus
is
unfavorable
for
renal
function
(Barsotti
et
al.
1984).
Therefore,
egg
white
should
be
used
in
clinical
investigation
of
selective
protein
restriction.
References
1)
Barsotti,
G.,
Gambertoglio,
J.
&
Morelli,
E.
(1984)
The
decline
of
renal
function
slowed
by
very
low
phosphrus
intake
in
chronic
renal
patients
following
a
low
protein
diet.
Clin.
Nephrol.,
21,
54-59.
2)
Bosch,
J.P.,
Saccaggi,
A.,
Lauer,
A.,
Ronco,
C.,
Belledonne,
M.
&
Glabman,
S.
(1983)
Renal
function
reserve
in
humans.
Am.
J.
Med.,
75,
943-950.
3)
Bosch,
J.P.,
Lauer,
A.
&
Glabman,
S.
(1984)
Short-term
protein
loading
in
assess-
Acute
Loading
with
Protein
from
Different
Sources
277
ment
of
patients
with
renal
disease.
Am.
J.
Med.,
77,
873-879.
4)
Bosch,
J.P.,
Lew,
S.,
Glabman,
S.
&
Lauer,
A.
(1986)
Renal
hemodynamic
changes
in
humans.
Am.
J.
Med.,
81,
809-815.
5)
Corvilain,
J.
&
Abramow,
M.
(1962)
Some
effects
of
human
growth
hormone
on
renal
hemodynamics
and
tubular
phosphate
transport
in
man.
J.
Clin.
Invest.,
41,
1230-
1235.
6)
Dhaene,
M.,
Sabot,
J.P.,
Philippart,
Y.,
Doutrelepont,
J.M.
&
Vanherweghem,
J.L.
(1987)
Effect
of
acute
protein
loads
from
different
sources
on
glomerular
filtration
rate.
Kidney
Int.,
32,
S25-S28.
7)
Evanoff,
G.,
Thompson,
C.,
Brown,
J.
&
Weinman,
E.
(1987)
The
effect
of
dietary
protein
restriction
on
the
progression
of
diabetic
nephropathy.
Arch.
Intern.
Med.,
147,
492-495.
8)
Fried,
T.A.
&
McCoy,
R.N.
(1986)
Effects
of
atriopepsin
II
on
determinants
of
glomerular
filtration
rate
in
the
in
vitro
perfused
dog
glomerulus.
Am.
J.
Physiol.,
250,
F1119-F1122.
9)
Gingliano,
D.,
Sicuranza,
G.,
Quarto,
E.
&
Quartieri,
J.
(1986)
Prevention
of
diabet-
ic
nephropathy
by
low-protein
alimentation.
In
:
Diabetic
Renal
Retinal
Syndrome,
Vol
3.
edited
by
E.A.
Friedman
&
F.A.
L'Esperance,
Jr.,
Grune
&
Stratton,
Orlando,
F.L.,
pp.
201-216.
10)
Greene,
S.A.,
Dalton,
R.N.,
Turner,
C.,
Haycock,
G.B.
&
Chantler,
C.
(1987)
Hyperg-
lycemia
with
and
without
glycosuria
Effect
on
inulin
and
para-amino
hippurate
clearance.
Kidney
Int.,
32,
896-899.
11)
Hostetter,
T.H.
(1986)
Human
renal
response
to
a
meat
meal.
Am.
J.
Med.,
77,873-
879.
12)
Ito,
S.,
Tsuda,
A.,
Momotsu,
T.,
Igarashi,
K.,
Kasahara,
S.,
Satoh,
K.
&
Shibata,
A.
(1989)
Urinary
orosomucoid
excretion
rate
in
patients
with
non-insulin-dependent
diabetes
mellitus.
Acta
Endocrinol.,
120,
584-590.
13)
Jones,
G.,
Lee,
K.
&
Swaminathan,
R.
(1985)
Glomerular
filtration
response
to
acute
protein
load.
Lancet,
2,
838.
14)
Kato,
H.,
Adachi,
N.,
Iwanaga,
S.,
Abe,
K.,
Takada,
K.,
Kimura,
T.
&
Sakakibara,
S.
(1980)
A
new
fluorogenic
substrate
method
for
the
estimation
of
kallikrein
in
urine.
J.
Biochem.,
87,
27-32.
15)
Kleinknecht,
C.,
Salusky,
I.
&
Broyer,
M.
(1979)
Effects
of
various
protein
diets
on
growth,
renal
fuction
and
survival
of
uremic
rats.
Kidney
Int.,
15,
534-541.
16)
Krishna,
G.G.,
Newell,
G.,
Miller,
E.,
Hegger,
P.,
Smith,
R.,
Polansky,
M.,
Kapoor,
S.
&
Hoeldtkt,
R.
(1988)
Protein-induced
glomerular
hyperfiltration
Role
of
hor-
monal
factors.
Kidney
Int.,
33,
578-583.
17)
Levy,
S.B.,
Lilley,
J.J.,
Frigon,
R.P.
&
Stone,
R.A.
(1977)
Urinary
kallikrein
and
plasma
renin
activity
as
determinants
of
renal
blood
flow.
J.
Clin.
Invest.,
60,
129-
136.
18)
Mogensen,
C.E.
(1971)
Glomerular
filtration
rate
and
renal
plasma
flow
in
short-term
and
long-term
juvenile
diabetes.
Scand.
J.
Clin.
Invest.,
28,
91-100.
19)
Mogensen,
C.E.
(1976)
Renal
fuction
changes
in
diabetes.
Diabetes,
25,
872-879.
20)
Motomura
K.,
Okida,
S.,
Sanai,
T.,
Ando,
T.,
Onoyama,
K.
&
Fujishima,
M.
(1988)
Importance
of
early
initiation
of
dietary
protein
restriction
for
the
prevention
of
experimental
renal
disease.
Nephron,
49,
144-149.
21)
Nakamura,
H.,
Takasawa,
M.,
Kasahara,
S.,
Tsuda,
A.,
Momotsu,
T.,
Ito,
S.
&
Shibata,
A.
(1989)
Effects
of
acute
protein
loads
of
different
sources
on
renal
function
of
patients
with
diabetic
nephropathy.
Tohoku
J.
Exp.
Med.,
159,
153-162.
22)
Parving,
Noer,
J.,
Kehlet,
H.,
Mogensen,
C.E.,
Svensen,
P.A.
&
Heding,
L.
(1977)
The
effect
of
short
term
glucagon
infusion
on
kidney
function
in
normal
man.
Diabetologia,
13,
323-325.
23)
Sugimoto,
H.
(1981)
Fundamental
and
clinical
studies
on
a
new
radioimmunoassay
278
H.
Nakamura
et
al.
kit
for
the
measurement
of
glucagon.
Horm.
Clin.
Res.,
29,
487-491.
(Japanese)
24)
Trevisan,
R.,
Nosadini,
R.,
Fioretto,
P.,
Avogaro,
A.,
Duner,
E.,
Jori,
E.,
Valerio,
A.,
Doria,
A.
&
Crepaldi,
G.
(1987)
Keton
bodies
increase
glomerular
filtration
rate
in
anormal
men
and
patients
with
type
1
(insulin-dependent)
diabetes
mellitus.
Diabetologia,
30,
214-221.
25)
Wiseman,
M.J.,
Dodds,
R.,
Bending,
J.J.
&
Viberti,
G.C.
(1987)
Dietary
protein
and
the
diabetic
kidney.
Diabetic
Med.,
4,
144-146.
26)
Yamaji,
T.,
Ishibashi,
M.
&
Takaku,
F.
(1985)
Atrial
natriuretic
factor
in
human
blood.
J.
Clin.
Invest.,
76,
1705-1709.